原发性胆汁性肝硬化（PBC）病因、发病机制未明，可能与遗传因素和环境因素导致的免疫异常密切相关。胆管上皮细胞（BEC）是PBC中唯一受累靶器官，TGF-β1信号转导异常与BEC损伤密切相关、同时也是肝星状细胞（HSC）活化最主要的诱导剂，而HSC又为肝纤维化发病的关键环节。因此，TGF-β1在PBC的发生发展中起重要作用。课题组前期研究取得了藏药郎庆阿塔的SFDA临床批件，临床及动物实验均发现郎庆阿塔治疗PBC有效。为进一步探寻其作用机制，课题组拟通过建立PBC模型小鼠，进行药效学评价，并利用Western blot、ELISA、免疫组化等方法研究TGF-β1等多个信号转导途径对BEC、HSC的调控，探寻其分子作用机制，为PBC提供理论依据和实验依据，也为PBC的治疗提供新的思路。

The etiology and pathogenesis of Primary biliary cirrhosis (PBC) is unknown , may be closely related to the immune abnormalities caused by genetic and environmental factors, biliary epithelial cells (BEC) is the only target organ affected in PBC. TGF - beta 1 signal conduction abnormalities are closely associated with the BEC damage ,as same as the main inducer of hepatic stellate cells (HSC) activation ,which is the key link in the process of liver fibrosis disease, and playing an important role in the occurrence and development of the PBC. Our group's early research has take the SFDA clinical entity of Lang Qing A Ta, the clinical and animal experiments have found that Lang Qing A Ta is a effective treatment of PBC. In order to further explore its action mechanism, our goup is going to establish the PBC model mice and evaluate the pharmacodynamic , and using Western blot, ELISA and immunohistochemical to study the regulation of BEC、HSC by TGF - beta 1 etc.,as well as exploring its molecular mechanism, thus providing the theoretical and experimental basis for the PBC and offering a new way for the treatment of PBC.

原发性胆汁性肝硬化（PBC）病因、发病机制未明，可能与遗传因素和环境因素导致的免疫异常密切相关。课题组前期研究取得了藏药郎庆阿塔的SFDA临床批件，临床及动物实验均发现郎庆阿塔治疗PBC有效。为进一步探寻其作用机制，本研究首先建立PBC动物模型，与人类PBC早期病变基本相似，为研究原发性胆汁性肝硬化的药物治疗提供了新的模型依据。第二部分药效研究，在动物模型建立后给予藏药郎庆阿塔治疗，显示出改善肝功能和病理及降低抗线粒体抗体（AMA/M2）滴度等优势，该治疗效果与阳性药（UDCA）组相近，为临床上治疗原发性胆汁性肝硬化提供了新思路。第三部分机制研究，进一步明确藏药郎庆阿塔含药血清对活化肝星状细胞增殖活动具有抑制作用，同时分析藏药郎庆阿塔治疗原发性胆汁性肝硬化作用途径，研究结果提示该作用机制之一是通过TGF-β/smad信号通路实现，为临床用药提供了科学依据。鉴于PBC发病机制尚未明确，目前临床疗效欠满意，攻克该难题是极待解决的科学问题，本研究通过挖掘藏医药精粹，利用先进的实验手段开展了系列体内外研究，其研究结果推广应用后，将产生巨大的社会效应和经济效应，并为民族医药的发展作出更大的贡献。